Chemical sensors, in particular silicon-based biosensors

ABSTRACT

A three-dimensional structure of porous silicon considerably improves the anchorage of sensor-active material such as, for example, enzymes, antibodies, etc., on or in the substrate surface of chemical sensors, in particular silicon-based biosensors. This structure is produced by means of suitable etching which forms pore apertures adapted to the penetrability of the sensor-active material. The pore walls advantageously receive a non-conductive boundary layer which consists of oxides of Si and/or Al or Ta or silicon nitride and are preferably 1-100 nm thick. The porous layer is advantageously between 10 nm and 100 μm thick and the pores are preferably in the form of branched ducts whose average diameter is 1 nm-10 μm and in particular 10-1000 nm. The sensor-active material can optionally be distributed in a glass, solid, plastics or polymer membrane.

SPECIFICATION CROSS REFERENCE TO RELATED APPLICATIONS

This application is a national stage of PCT/DE95/01056 filed Aug. 9,1995 and based, in turn, on German National application P4427921.3 filedAug. 6, 1994 under the International Convention.

FIELD OF THE INVENTION

The invention relates to chemical sensors, in particular biosensors,which are silicon-based with a sensor-active coating on a semiconductivesubstrate functioning as a transducer.

BACKGROUND OF THE INVENTION

Chemical sensors and, especially biosensors operating with bioactivecomponents are known and are the subject of vigorous development.

Such sensors basically include a surface layer with a sensor-activematerial which is exposed to the medium to be tested, especially aliquid. This layer contains the sensor-active material which can beimmobilized, for example, in a membrane composed of polyvinylchloride.The signals supplied by the sensor-active material under the effect ofan analyte are transformed by a transducer element and are acquired inregistrable form by electronic signal processing which can be providedby integrated electronics.

As transducers, particularly semiconductive electrodes, field-effecttransistors, potentiometric and amperometric electrodes and the like areconsidered.

All known sensors have the common characteristic that they generallyhave insufficient adhesion of the sensor membrane on the respective baseelement, i.e. the measurement solution can wash it away or penetrate ina detrimental manner directly into the sensor membrane and damage itirreversibly. Connected therewith are stability problems and driftproblems with respect to the sensor output signals. Furthermore, thereis the need to establish the out-diffusion, i.e. the bleeding or washingout, of sensitive membrane components into the solution. Such sensors,as a consequence have only a limited life. It is also a drawback thatthe contacts and signal electronics are only separated by a thinpassivation layer from the sensitive region and thus the sensor ishighly prone to damage.

An attempt to solve this problem is described by Knoll in DE 41 15 414A1. Here, anisotropic etch pits are incorporated in the substratematerial as containments in which the sensor membrane can be anchored.The containments can be jacketed in a nonconductive material andadditionally, conductive electrodes can be deposited. These verticalcontainments comprise openings converging toward the rear side of thechips which are in direct contact with the measurement solution. As aconsequence, the above-described drawbacks are overcome. Especiallyso-called sensor arrays can be realized with this technique withdifferent sensitivities to different substances or ion types.

With this kind of sensor, the containment formation affords a certainprotection of the ion selective membrane to limit bleeding out anddissolution. This technology is however only apparently simple in thatit can be realized only with expensive lithography techniques.

OBJECT OF THE INVENTION

It is an object of the invention, therefore, to provide a sensor of theinitially described type, by which the sensor-active material can bedeposited in different forms on a different types oftransducer/electronic structures of the sensor with reduced tendencytoward damage, with stability enhancement and sensitivity increase.

SUMMARY OF THE INVENTION

This object is achieved with a silicon-based biosensor with asensor-active coating on a semiconductor substrate effective as atransducer. According to the invention the sensor-active material isreceived in the pores of a porous layer produced by an etching treatmentof the substrate surface and whose opening widths are matched to thepenetration characteristics of the sensor-active material. Anonconducting boundary layer can be provided on the pore walls. Theboundary layer between the surfaces of the porous material and thesensor-active material of silicon dioxide and/or aluminum oxide,tantalum pentoxide or silicon nitride. The nonconducting boundary layercan have a thickness of 1-100 nm. The porous layer can be a sponge-likelayer with mesopores and/or macro pores. The pores can be formed aspassages with branches with a mean pore diameter of 1 nm-10 μm,especially 10-1000 nm. The thickness of the foam-like layer can be 10nm-100 μm. The active material can be an adsorptive sensor-activematerial incorporated in or on the foam structure and bonded by acovalent bonding of the sensor-active material to the porous layerstructure.

There can also be a cross-linking of the biomolecules of thesensor-active material engaged in the pores. The sensor-active materialcan be distributed within a layer former such as a glass or solid orplastic or polymer member. The sensors of the invention can beion-selective electrodes, capacitive field effect structures, ionsensitive field effect transistors, or an array of elements of differentsensitivity. These sensors are especially realizable in miniatured form.

According to the invention the use porous layer eliminates the need forexpensive lithography. The produced three-dimensional sponge structureserves as a matrix for a good mechanical anchoring and spatialcross-linking of the sensor-active materials in the porous semiconductorsubstrate. One can thus achieve a high physical (mechanical) andelectromechanical stability under liquid. This permits the use of thesensor especially in throughflow operations, for example, as a detectorin an FIA system.

Indeed the generation of porous silicon by an etching treatment has longbeen known as is also its use in biosensor technology according to JP61-218 932 A from 1986. In this system an ISFET is described on whosesurface, between source and drain, an insulating layer is generated andthen coated with polycrystalline silicon, which by anodic treatment isconverted into a porous silicon layer with a "film" for a biochemicalsubstance. This proposal has not found effect in the improved formationof biosensors and has not been used in practice as can be understoodfrom the proposal of Knoll. The present invention differs from thesubject of this Japanese open application in that the semiconductorsubstrate effective as the transducer is directly subjected to anetching treatment to generate a porous sponge structure opening from thesurface into the material, whose pores have a mean pore diameter whichmatches the penetration requirements for the sensor-active material.

Preferably sponge-like porous layers with mesopores and/or macroporesreceive the sensor-active material, especially via the intermediary of anonconductive insulating layer of reduced thickness, such that theeffectivity of the sensor-active material per unit area (geometric area)is thereby significantly increased.

The type and form of the sensor-active material determines naturally therequisite sponge structure of the porous silicon which is produced bythe etching treatment.

Basically one obtains after doping, different porosity profiles wherebyin n-silicon, deep etching channels are formed which are provided withbranches and whose mean pore diameter is determined by the selectedparameters of pretreatment, temperature, composition of the electrolyte,anodization current density and anodization duration as well asposttreatment. By illumination, i.e. exposure to light, during theanodic etching treatment, the pore formation can be influenced, whereby,especially by intermittent light impingement optionally desirablediameter variations in pore passage over the length of the pore can beachieved.

The porous structure which results from etching of p-silicon as well asn+silicon or p+silicon (microporous or with so-called herring-bonebranching) can be selected by the choice of the type of sensor-activematerial which is to be applied. A detailed collection of etchingconditions and etching results can be found in R. L. Smith and S. D.Collins in J. Appl. Phys. 71 R1 of 1992.

One can distinguish, based upon the pore diameter of the produced spongestructure, between microporous silicon (pores of a diameter less than 2nm), mesoporous silicon (pores of a diameter of 2-50 nm) and macroporoussilicon (pores of a diameter greater than 50 nm). For the processparameters which can be varied for the etching treatment of theinvention, use of the following especially can be made:

the electromechanical pretreatment of the semiconductive substrate(hydrofluoric acid, organic or inorganic solvents, water, as well astheir mixtures);

the etching medium and solvent medium used (HF-ethanol or HF propanolmixtures);

the process temperature (5°-150° C.);

the anodization current (1-500 mA/cm²);

the additional illumination during the anodization (wavelength λ=200-800nm, intensity or power: 0.1-100 mW/cmz, distance of the lamp from theupper surface of the specimen or the specimen underside as well as thefrequency of the illumination f=0.1-1000 Hz);

the posttreatment of the porous sponge structure (flushing regimen, e.g.in ethanol/temperature/storage conditions, e.g. in N₂ atmosphere).

The preferred nonconducting layer on the porous walls of the Si spongestructure to be generated can be SiO₂ or another dielectric component,like Al₂ O₃ or Ta₂ O₅ or ZrO₂, Si₃ N₄ silicates, glasses, etc.,individually or in combination. In the case of SiO₂, the Si surfaceprovided in the sponge structure is intentionally oxidized. This ispreferably achieved by a uniform thermal, anodic, chemical or naturaloxidation. The layer thickness of the resulting nonconductive layer canthus vary, depending upon the pore size, within the range of 1 to 100nm.

In the case of Al₂ O₃ or Ta₂ O₃ the base metal (Al or Ta) is at leastinitially electrochemically deposited galvanically or deposited from thegas phase and then converted into the corresponding oxide. Thedeposition of oxidic dielectric compounds like SiO₂, Al₂ O₃, Ta₂ O₅,ZrO₂, Si₃ N₄, etc. by conventional PVD processes or CVD processesdirectly upon a silicon substrate is also known (L. Bousse et al,Sensors and Actuators, Vol. 17 (1994), 157-164).

Sensor active materials which can be anchored in or on the so formedporous structure according to the invention are known in large number.For example, different systems are given below together with thesuitable porosity of the silicon as well as the type of anchoring.

Apart from pure adsorption or chemisorption, it appears that a covalentbonding of sensor-active material to the porous structure is suitablewhen the mean pore diameter is selected between 10 and 10³ nm. The poresurfaces can be activated by chemical pretreatment or modification, e.g.silanization, for the bonding of sensor-active material. Furthermore,so-called functional cross linkers (spacer molecules) like, for example,glutaraldehyde, can be anchored to the pore boundary surfaces or walls.

A complete or partial cross-linking (for example only in the regionclose to the surfaces) between the biomolecules which are incorporatedin the porous layer with one another, for example, with glutaraldehyde,can afford an especially stable integration of the biomaterials in thelayer. Such a cross-linking can be achieved after incorporation of thebiomolecules in the porous layer, for example, by exposure to agluteraldealdehyde saturated atmosphere. The mean pore diameter of theso-treated layer should be greater than or approximately equal to 50 nm.

Biological structures, like enzymes, proteins, antibodies, cells,organelles, tissue segments, etc. can be incorporated directly or bymeans of gel inclusion, i.e. embedded in a carrier matrix of polymers,like polyurethane, polyacrylamide, agar-agar, gelatin, etc., optionallyspatially cross-linked, whereby depending upon the size of the materialto be included in the porous sponge structure, a mean pore size in therange of 10 nm to 100 μm, especially greater than or approximately equalto 20 nm, can be chosen.

For the anchoring of sensor-active materials in the form of liquidmembranes, which, as "membrane cocktails," are comprised for example ofpolyvinylchloride, plasticizers, ion-active compounds (ionophores, andadditives, pore sizes of at least 50 nm, preferably over 100 nm areprovided.

Especially for chemosensors, glass layers are suitable which as liquidsol/gel layers+wetting agents are incorporated in the pores, withsubsequent temperature treatment to an amorphous glass layer which canbe suitable, dependent on the starting cocktail, for the detection ofdifferent alkali ions. For this purpose, pore sizes of greater than orapproximately equal to 50 nm, especially in excess of 100 nm, aresuitable. Solid layers of galvanically deposited metal or metaldeposited from the gas phase and also electrochemically in the porousmaterial, combined with metal compounds (like for example Ag/AgCl, etc.)which are useful for the detection of anions and have proved with theaforedescribed pore sizes to be extraordinarily flexible, whereby poresizes in the range of 1- to 500 nm are especially suitable.

The sensor substances which are chosen can, in known manner, be combinedfrom different sensor types: further details are found in theliterature, for example in F. Sheller, F. Shubert, "Biosensors", AcademyPublishers, Berlin 1989.

BRIEF DESCRIPTION OF THE DRAWING

The above and other objects, features, and advantages will become morereadily apparent from the following description, reference being made tothe accompanying drawing in which:

FIG. 1, and 1a are cross sections of a porous (bio) chemical siliconsensor, FIG. 1a being an enlargement of a portion of FIG. 1;

FIG. 2 is a section of a capacitative field effect sensor;

FIG. 3 is a section through a field effect sensor;

FIG. 4 is section through a potentiometrically operating ion selectiveelectrode (ISE); and

FIGS. 4A and 4B are sections of details of other embodiments,

FIG. 5 is a section showing a sensor array.

SPECIFIC DESCRIPTION

FIG. 1 and 1a shows in cross section the layer structure of the porous(bio)chemical silicon sensor.

As the base material 2, a doped monocrystalline or polycrystallinesilicon is used. The doping concentration varies in the range between1×10¹⁴ -1×10¹⁸ /cm³ for n- or p-silicon and is greater than 1×10¹⁸ /cm³for n+- or p+-silicon. The underside of the base material 2 has an ohmicbackside contact 1 comprised of a conducting layer or layer sequence, offor example A1, Ti/Pt/Au, Cr/Sb/Au or a similar conducting combination.This contact layer can be produced by means of conventional coatingprocesses, like PVD deposition and ion implantation or byelectrochemical deposition processes.

To produce the porous layer structure, the base substrate is built intoa chemically inert sample cell (for example of Teflon) and the probe isconnected as an anode against a cathode immersed in the etchingsolution, the cathode being for example of platinum, and a sponge orfoam structure 3 generated in the following manner:

(a) If n-silicon is used as a starting material, depending upon theillumination intensity and the side of illumination, different types ofpore structure and channel structure can result. If the source, forexample, a halogen lamp, is on the side opposite side 1, in the bulk ofthe n-silicon, vertical macroporous channels are formed (lengthcorresponding to the layer thickness of the porous structure, diameter:0.1 to 10 μm) with horizontal lateral branchings 3, i.e. so-called sidebranches of comparable dimensions. Thereabove, there is formed in thesurface region a microporous layer as isotropic pore structure(diameter: less than 5 nm), which in combination with the macroporousfoam structure 3 is used or after the conclusion of processing can beremoved with a NaOH solution. Both the energization current density(increase in the porosity) and also the treatment time (increase in thelayer thickness of the porous silicon structure) determine theconfiguration of this macroporous sponge structure. The layer thicknessof the microporous layer parallel thereto is substantially determined bythe light penetration depth, i.e. the wavelength of the illuminationsource.

If the intensity of the illumination source is changed, in addition,with time, i.e. if during the pore growth for example, the light sourceis switched on and off, then the diameter of the vertical passage isadditionally modified. During the illumination phase another porediameter is formed than during the period of the dark phase. The resultis a wave-like bulgy vertical pore and channel structure which supportsthe mechanical anchoring of the specifically disposed sensor membrane.If the light source is found on the side 1, the macropores are formed asvertical passage structures without laterally branchings. Depending uponthe process parameters, the pore diameter then varies between 100 nm and10 μm. The length of these vertical passages lies in the range of thetotal layer thickness of the porous layer.

(b) In contrast thereto, n-silicon forms a mesoporous foam structure(pore diameter: 2-50 nm, passage length corresponding to the layerthickness of the porous structure). The horizontal branchings do notextend strictly orthogonal to the vertical passages. The porous layerstructure is comparable to a herring-bone pattern, i.e. the sidebranches are inclined by less than 45° with respect to the verticalpassages.

(c) Microporous layer structures (mean pore diameter less than 2 nm) canbe realized above all with p-silicon as the starting material. In thiscase, there is formed an isotropic homogeneously distributed porestructure. The pore diameter can in the above-indicated range be set bythe illumination. The porosity is adjustable by variation of theanodization current.

(d) If a p+-doped silicon is used as the base material, the thusproduced foam or sponge structure is comparable with the results forn+-doped silicon. The horizontal transverse branching correspondsentirely analogously in its dimensions to the construction describedunder (b). Moreover the vertical pore diameter as well as the passagelengths are comparable in their geometric extents.

The foam or sponge structure which can be variably set under points(a)-(d), opens up the possibility of a targeted tailoring of the sensoractive (bio-)chemical membrane. For this purpose, the foam structure 3(shown in FIG. 1a) is coated with a nonconductive material 4. The thusformed porous layer serves to receive the sensor-active components 5.

Depending upon the respective function, the sensor-active material can,as has already been described at the outset, be provided in the form ofan ion selective membrane or also in the form of biosensor elements,whereby, depending upon requirements, a chemical pretreatment (forexample by silanization) can be provided to produce a good, directbonding of the sensor materials on or in the porous layer:

(a) The known production of ion selective membranes can be transferredin the same type and manner also to the porous foam structure. For thispurpose, membrane material contained in a solvent (for exampleionophore, plasticizer, PVC matrix) can be incorporated in the foamstructure in which, after evaporation of the solvent, a stabilizationand solidification occurs.

(b) Alternatively there is a further possibility of depositingbiomolecules in the form of enzymes, antibodies-antigens, tissuesegments, organelles or receptors as sensor-active membrane componentsor directly in the foam structure. For this purpose, physical (e.g.adsorption, gel inclusion) and also known chemical immobilizationprocesses (e.g. covalent bonding, cross linking) can be used.

FIG. 2 shows, as an example, the production of a (bio-)chemical porouscapacitive field effect sensor. The layer structure corresponds to thearrangement described in FIG. 1. The sensor active material 6,optionally provided in the form of a membrane, can function both as achemosensor and also as a biosensor depending upon the respective layercomposition. Furthermore, there is a possibility that sensor-activematerials 6 will deposit in the foam structure and optionallyadditionally on the sensor surface. The porous sensor element isencapsulated in an appropriate measurement cell 8 (for example of Teflonor PMMA) and is brought directly into contact with the anolyte solution7. It is also conceivable to provide an encapsulation which correspondsto the construction shown in FIG. 3 and described below.

To produce the electrical connection between the anolyte cells 7 and themetallic substrate contact 1, for example, a constant potentialcommercially available reference electrode can be incorporated in 7 andconnected with 1. Instead of the latter, it is also possible to use anidentical nonsensitive porous sensor element as the reference element.In this case, there is the advantage of an arrangement primarily inminiaturization which as a rule is limited by the size of the referenceelectrode and with a reduced effect of external influences like, forexample, different temperature coefficients of the sensor element andthe reference electrode.

FIG. 3 shows the construction of a porous (bio-) chemical field effecttransistor. The base material used corresponds to that of theabove-described capacitive silicon sensor. Depending upon the doping ofthe base material 2, the two pockets, source and drain 10, have theopposite doping. If the base material is n-doped, the source and drainare p-doped and vise versa. These are connected with a fixed support,for example, a printed circuit board substrate 13, via a metal contact11 (for example Ti/Al, Ti/Pd/Au, or other conducting material). Themetallization 11 is insulated from the base substrate by an insulatorlayer or layer sequence 9 and 9a of SiO₂ or SiO₂ /Si₃ N₄ or SiO₂ /Al₂ O₃or SiO₂ /Ta₂ O₅ etc. The production of such field effect transistors isknown from the literature (K. Horninger, Integrated MOS Circuits,Springer Verlag (1987) Heidelberg).

New in this arrangement is the use of the gate region between the twopockets 10 in the form of a porous silicon gate. For that, during theappropriate processing, i.e. directly after the doping of both pockets10, a "projecting" gate is produced as shown in the Figure, for exampleby an additional photolithographic and etching step. Alternatively, sucha gate can be realized also by means of a process used in semiconductivetechnology like, for example, epitaxy, etc.

The generation of the foam structure 3 in the silicon starting materialor subsequent deposition of the sensor active material in conjunctiontherewith are effected in exactly analogous manner as described inFIG. 1. The substrate contact 1 for the base carrier 13 is realized by aconductive adhesive bonding 14, for example, with conductive silver. Thesensor component is protected with a protective layer 12, of forexample, epoxy resin or another potting material against the measurementenvironment so that only the sensor active gate region can contact theanolyte solution. The encapsulation can, however, also be effected bymeans of incorporation in a fixed probe cell as described in FIG. 2. Thepossibility, similar to that of the capacitive porous (bio-)chemicalsensor to introduce a nonsensitive sensor element directly instead of anexternal reference electrode is also a solution with this construction,the reference electrode having the form of a reference transistor.

An embodiment in the form of a porous potentiometric (bio-)chemical ionselective electrode (ISE) is apparent from FIG. 4. The production of theporous foam structure and its sheathing with a nonconductive material iseffected in an analogous way to that described under FIG. 1. Inconnection therewith, the base substrate 2 from the probe back side 1 isetched away until the region of the foam structure by a wet chemicalprocess, for example by means of a HF/water mixture, so that the foamstructure is liberated on the back side of the probe.

Before the sensor active components 6 as solid or liquid electrolyte inan exactly analogous way as described under FIG. 1, are incorporated inthe foam structure, the metallic conductors must be realized as isindicated in FIGS. 4A or 4B. Thus in FIG. 4A a metal film 17, forexample of Ag, is deposited in the pore structure by means ofconventional PVD processes, (for example by evaporation). Thechloridization of this Ag layer by means of known electrochemicalprocesses is effected directly following. An additional internalelectrolyte is introduced in FIG. 4B. This comprises as a rule a highmolecular salt solution, for example saturated KCl solution whichremains as an internal electrolyte after evaporation of the solvent whenintroduced in a solid organic matrix, for example, gelatin.

The so processed semiconductive structure is fixed by means of aconductive adhesive bond 14, e.g. conductive silver on a carrier 16(FIG. 4) with electric contacts, for example from glass, plastic,silicon or ceramic. The thin porous silicon structure is therebystabilized on the carrier 16. The processing of the sensor active layeris effected as has already been set out under FIG. 1. The completedporous ISE is applied to a holder 16 of solvent resistant material withelectric contacting, for example, Teflon or plastic. The sensorcomponent is protected against the measurement environment by means of aprotective layer 12 of, for example, epoxy resin so that only the sensoractive region of the porous ISE contacts the anolyte solution.

FIG. 5 shows the arrangement of a (bio-)chemical porous semiconductorsensor as a multisensor in the form of a sensor array arrangement. Hereare illustrated porous sensors 19 of different sensitivity within onesilicon substrate 2. Thus in a first step via a simple photolithographicstructuring the number of sensor elements (for example four variablesensors) is established. Thereafter, the individual porous foamstructures corresponding in number are produced by the above-indicatedprocess steps to sensor elements. Depending upon the respective use,sensor elements as described in FIG. 2, FIG. 3, FIG. 4 are realized. Thesensor elements are encapsulated or incorporated in a fixed housingentirely analogously in kind and manner in a probe cell.

We claim:
 1. A chemical sensor which comprises:a body of silicon etchedfrom an active surface thereof to form a pore network penetrating intosaid body from said active surface and forming a foam structure fromsaid body at least along said surface; a layer of at least one reactivematerial in said foam structure and lining pores thereof, whereby saidlayer can contact and react with an environment to alter conductivitycharacteristics of said body; and at least one electrode in contact witha surface of said body opposite said active surface for electricalmeasurement of altered conductivity of said body, said pores having poreopenings selected to enable said pores to accommodate said material. 2.The chemical sensor defined in claim 1, further comprising a boundarylayer on walls of said pores between said body of silicon and saidreactive material, said boundary layer having a thickness ofsubstantially 1 to 100 nm and being selected from the group consistingof silicon dioxide, aluminum oxide, tantalum oxide, silicon nitride andmixtures thereof.
 3. The chemical sensor defined in claim 1 wherein saidfoam structure has a thickness of 10 mm to 100 μm and said pores arepassages with branches having a mean pore diameter of 1 nm to 10 μm. 4.The chemical sensor defined in claim 1 wherein said reactive material isadsorbed on said body of silicon in said pores.
 5. The chemical sensordefined in claim 1 wherein said reactive material has biologicallyactive molecules cross linked to a substance in said pores.
 6. Thechemical sensor defined in claim 1 wherein said reactive material is abiologically active material distributed within a layer formerconstituted as glass or a polymeric membrane.
 7. The chemical sensordefined in claim 1 constituted as an element of an ion selectiveelectrode.
 8. The chemical sensor defined in claim 1 constituted as anelement of a capacitative field effect transistor.
 9. The chemicalsensor defined in claim 1 wherein said sensor is part of an array ofsaid sensors with each of said sensors being of a sensitivity differentfrom that of others of said sensors.
 10. A method of making a chemicalsensor which comprises the steps of:a) etching a body of silicon from anactive surface thereof to form a pore network penetrating into said bodyfrom said active surface and forming a foam structure from said body atleast along said surface with a thickness of 10 nm to 100 μm, said porestructure being constituted of branched pores having a mean porediameter of 1 nm to 10 nm; b) lining said pores with a nonconductingboundary layer selected from the Group which consists of silicondioxide, aluminum oxide, tantalum oxide, silicon nitride and mixturesthereof, said boundary layer having a thickness of 1 to 100 nm; c)depositing in said pores at least one reactive material in a layer whichcan contact and react with an environment to alter conductivitycharacteristics of said body; and d) applying to said body at least oneelectrode in contact with a surface of said body opposite said activesurface for electrical measurement of altered conductivity of said body,said pores having pore openings selected to enable said pores toaccommodate said material.
 11. A method of making a chemical sensordefined in claim 10, further comprising the step of forming saidmaterial by incorporating a bioactive substance in a layer formingmaterial selected from the Group which consists of glass and polymers.